NSC 652287D showed potent differential growth inhibitory activity against selected renal, ovarian, colon and lung human tumor cell lines in the NCI primary in vitro anticancer drug screen. Intraperitoneal administration of 200 mg/kg by different schedules to mice bearing subcutaneously implanted early stage xenografts of the A498 renal line resulted in a high percentage of tumor free animals after four weeks. Based upon the in vivo efficacy and its novel structure, NSC 652287D was selected for preclinical evaluation by the DCT Decision Network Committee. The objectives of this project were to develop an analytical method for the assay of NSC 652287D in biological fluids and to define the in vivo pharmacokinetic properties of the compound in order to provide an objective basis for selection and optimization of the route of administration, dose and dose schedule. Plasma concentration-time profiles following IV injection of 100 micro m/kg (29 mg/kg) in mice and 30 micro m/kg (9 mg/kg) in a dog were fitted by computerized nonlinear regression analysis. Profiles exhibited triexponential behavior in both the mouse and the dog. Initial half-lives were rapid (approximately 2 minutes) indicating rapid distribution into tissues. Terminal half-lives were several hours. Clearance from the plasma was extremely rapid in both species, and the very high total body volumes of distribution (116 and 868 l/kg for the mouse and dog respectively) suggest that the compound is highly distributed into deep tissue compartments. Following IP or oral dosing, plasma concentrations of NSC 652287D fluctuated, but appeared to decline slowly during 24 hours after dosing. Concentrations were sustained between approximately 10 and 30 nM (3 and 10 ng/ml) for 24 hours. These plasma concentrations are in the range of those which resulted in growth inhibition of the sensitive cell lines in vitro.